Poor solubility of therapeutic agents is widely recognized as a serious issue that limits the effective administration of such compounds to the mammal in need thereof. One common approach to manage this problem is chemical derivatization of the compounds to form a prodrug, i.e. drug derivative that releases the parent active entity upon its administration, as reviewed, for example, by Ettmayer et al. in J. Med. Chem., 2004, p. 2393.
A limited number of effective prodrugs are known for NH-containing compounds, as noted, for example, by Stella et al. in Bioorg. Med. Chem. Lett., 2007, p. 4910. Amongst antibacterial agents, the prodrug of antibiotic ceftaroline, ceftaroline fosamil (described, for example, by Ge et al. in Antimicrob. Agents Chemotherapy, 2010, p. 912), is an example of a sole approved prodrug of the phosphoramidate class of N-phosphorylated amines.
Among newer antibacterials, oxazolidinone compounds are a class of antimicrobials active against all key gram-positive pathogens. Representative antibacterial agents of this class include linezolid (ZyvoxR), which is used for a treatment of key gram-positive infections.
As for many other pharmaceuticals, it is important that the oxazolidinone agent has sufficient solubility for its convenient administration in a liquid form. Thus, a modest solubility of linezolid requires a slow twice-daily intravenous infusion, since the single liquid drug dose of 600 mg is formulated in a relatively large volume of 300 cc.
None of aforementioned publications specifically contemplates compounds provided herein, their beneficial physico-chemical profiles, their combination therapies, or compositions thereof.